Platform program for evaluating treatments in metastatic HER2-positive breast cancer

PRE-Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis: A Phase I/Ib Platform Trial

This study is testing different new treatments for people with advanced HER2-positive breast cancer to see which ones work best before moving them to larger trials.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 124 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: QuantumLeap Healthcare Collaborative (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 7 sites (Birmingham, Alabama and 6 other locations)
• Trial ID: NCT05868226 on ClinicalTrials.gov

What this trial studies

The PRE-I-SPY Phase I/Ib program is an open-label, multisite platform trial aimed at assessing various single agents and combinations for treating metastatic HER2-positive breast cancer. The study includes multiple drug regimen arms, each with a dose-finding group followed by a dose-expansion group. Eligibility criteria may vary based on the specific treatment arm, allowing for a tailored approach to patient selection. The goal is to efficiently move promising treatments into further testing in the I-SPY 2 SMART Design Trial and other oncology trials within 12 to 18 months.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a diagnosis of metastatic HER2-positive breast cancer and adequate organ function.

Not a fit: Patients with non-HER2-positive breast cancer or those with severe organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this program could lead to more effective treatment options for patients with metastatic HER2-positive breast cancer.

How similar studies have performed: Other studies utilizing platform trial designs have shown promise in advancing treatment options for various cancers, indicating a potential for success in this approach.

Eligibility criteria

General Inclusion Criteria (GIC):

* GIC1: The participant must have ability to understand and willingness to provide signed written informed consent prior to any study related assessments and procedures and for collection of archival FFPE blocks (freshly cut 14 unstained tumor slides would be acceptable).
* GIC2: Age ≥ 18 years at the time of signing the informed consent
* GIC3: Gender: Male or female (premenopausal and postmenopausal)
* GIC4: ECOG performance status Grade 0-2
* GIC5: Estimated life expectancy \> 12 weeks at the start of investigational medicinal product (IMP) treatment.
* GIC6: Adequate organ function, evidenced by the following laboratory results within 30 days of the start of IMP:

  * Absolute neutrophil count ≥ 1,500/mm3
  * Platelet count ≥ 100,000/mm3
  * Hemoglobin ≥ 9.0 g/dL with no blood transfusion in the past 28 days
  * Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
  * Estimated Creatinine clearance (using Cockcroft-Gault formula) ≥ 60 mL/min for small molecules and \>30 mL/min for monoclonal antibodies unless otherwise specified in the Arm Specific Eligibility.

These cut-off values may be modified with supporting data for specific drug regimens.

* GIC7: Non-Pregnant: Serum or urine pregnancy test must be negative within 14 days of IMP treatment start in women of childbearing potential. Pregnancy testing does not need to be pursued in patients who are judged as postmenopausal before enrollment, or who have undergone bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation. If male, they must agree to refrain from donating sperm during treatment.
* GIC8: Contraception: Women of childbearing potential and men must be willing to use adequate contraception for the duration of protocol treatment. Additional information regarding contraception for the specific treatment arm will be added to the drug arm description. Adequate contraception is defined as one highly effective form (i.e., abstinence, (fe)male sterilization) OR two effective forms (e.g., non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream / suppository).
* GIC9: Prior therapy effects: Resolution of all acute toxic effects of prior therapy, including radiotherapy, to grade ≤1 and neuropathy to grade ≤2 (except toxicities not considered a safety risk for the patient) and recovery from surgical procedures.
* GIC10: Participant compliance: Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
* Additional arm specific inclusion criteria as needed by drug arm regimen

General Exclusion Criteria (GEC):

* GEC1: Wash out periods: No other anticancer therapy within the following periods:

  * chemotherapy or investigational agents, 3 weeks
  * mitomycin C and nitrosoureas, 6 weeks
  * radiotherapy, 3 weeks
  * targeted therapy, 2 weeks
  * MAbs, ADCs, and immunotherapy, 3 weeks
  * endocrine therapy, no washout needed
* GEC2: Concurrent therapy with other Investigational Products.
* GEC3: Prior history of drug/regimen hypersensitivity: History of infusion-related reactions and/or hypersensitivity to IMP or excipients of the study drug/drugs which led to permanent discontinuation of the treatment.
* GEC4: Uncontrolled intercurrent illness including (active infection, diabetes, pulmonary embolism in the past 6 months, or psychiatric illness/social situations that would limit compliance with study requirements).
* GEC5: Cardiovascular disease: History (within 6 months prior to start IMP) of clinically significant cardiovascular disease such as unstable angina, congestive heart failure (CHF), myocardial infarction, uncontrolled hypertension, cardiac arrhythmia requiring medication, or baseline corrected QT by Fridericia's formula (QTcF) length \> 470 msec for men and women. The QTcF cut-off value may be modified with supporting data for specific drug regimens.
* GEC6: CNS tumoral spread: Active uncontrolled/symptomatic central nervous system cancer/spinal cord compression. Previously treated and clinically stable lesions, as per Investigator's judgment, are permitted. Newly discovered asymptomatic lesions that are not life threatening and do not require urgent local treatment to ensure patient safety, after consultation with study regimen chaperones, may be permitted.
* GEC7: Liver disease: Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis.
* GEC8: Recent major surgery within 4 weeks prior to start IMP treatment
* GEC9: Pregnancy or breastfeeding
* GEC10: Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
* GEC11: Other conditions, which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to complete the study.
* GEC12: Concomitant malignancies: A diagnosis of a malignancy in the 2 years prior to starting study treatment other than the disease under study. Exceptions include indolent or definitively treated malignancy not expected to require treatment during the study, affect the safety of subjects, or affect the endpoints of the trial.
* Additional arm specific exclusion criteria as needed by drug arm regimen

Where this trial is running

Birmingham, Alabama and 6 other locations

• The University of Alabama at Birmingham O'Neal Comprehensive Cancer Center — Birmingham, Alabama, United States (Recruiting)
• Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)
• The University of Chicago Medicine Comprehensive Cancer Center — Chicago, Illinois, United States (Recruiting)
• UChicago Medicine Comprehensive Cancer Center at Silver Cross Hospital — New Lenox, Illinois, United States (Recruiting)
• UChicago Medicine Orland Park — Orland Park, Illinois, United States (Recruiting)
• University of Minnesota Masonic Cancer Center — Minneapolis, Minnesota, United States (Recruiting)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Paula R Pohlmann, MD, MSc, PhD — M.D. Anderson Cancer Center
• Study coordinator: Smita M Asare

Conditions HER2-positive Breast Cancer; Metastatic Cancer; Metastatic Breast Cancer; Metastatic; HER2-positive Metastatic Breast Cancer; HER2 Mutation-Related Tumors; HER-2 Protein Overexpression; HER2-negative Breast Cancer